The hormones of the female reproductive system have been implicated in the development of breast cancer and other gynecologic neoplasms and conditions by numerous basic, clinical, and epidemiologic studies. Our analysis of available information has led us to the testable hypothesis that breast cancer, and possibly other hormonally-related diseases, is related to menstrual cycle patterns and aberrations characterized by adequate estrogenic but inadequate progestational activity. Our current activities have demonstrated this hormonal pattern in women with abnormal cycles, including those at the time of menarche and menopause and in situations of amenorrhea, and infertility. With the use of the large, existing cohort study of detailed menstrual and reproductive events and a case-control study of women with breast cancer, we are currently testing this major hypothesis. In this proposed renewal, we wish to complete these epidemiologic studies and complex analytic activities, and to further exploit the existing data base to explore the antecedents of benign breast and gynecologic conditions. This further definition of the epidemiologic and physiologic correlates of these conditions will hopefully lead to better definition and prediction of those at risk, a better understanding of pathophysiologic mechanisms, and development of possible advances in prevention and early detection.